Ninety outbred white adult female mice were infected with Trypanosoma brucei gambiense (GUMS 2, alias LUMP 1237) originating from a Zairian patient and known to produce a low parasitaemia in rodents. The development of cerebral trypanosomiasis was independent upon the number of parasites inoculated per mouse. Trypanosomes appeared in the circulating blood about four months after infection, when some mice started to show the first signs of paresis which subsequently led to cachexia. A clinical test to stage such a development is described. 57 mice were sacrificed at various intervals after infection, starting from one to 22 months. The morphological changes in the brain consisted of a diffuse meningoencephalitis in 45 mice, (78.9%) often associated with parasites, the latter being best visualised in 21 mice (36.8%) by immunofluorescence using a specific antitrypanosome antibody. The trypanosomes showed a predominantly extravascular distribution in the cerebral parenchyma, to a lesser extent in the meninges and only rarely in the choroid plexuses. Deposits of immunoglobulins in the choroid plexuses and cerebral infiltrations by plasma cells were mild. The level of circulating immune complexes was found to be increased. Adequate intravenous Melarsoprol did not prevent the disease from progressing to advanced stages, and there is limited morphological evidence that it did not eradicate the parasite from the host. The immunofluorescent use of an antitrypanosome antibody to demonstrate the persistence of tissue parasites after chemotherapy is recommended. Murine models seem therefore to be suitable for drug screening in cerebral trypanosomiasis since all three trypanosomes of the brucei group can be adapted to mice.